1. Technical Field
The invention relates to methods and materials involved in the treatment of various diseases such as infections and IgE-related diseases. Specifically, the invention relates to methods and materials that can be used to vaccinate a mammal against specific self or non-self antigens. For example, the methods and materials described herein can be used to reduce the effects of IgE antibodies within a mammal.
2. Background Information
Mammals are susceptible to many diseases and illnesses including bacterial infections, viral infections, and IgE-related diseases such as allergies. In general, infections are characterized by the invasion and multiplication of microorganisms (e.g., bacteria, fungi, and viruses) within body tissues. Many types of infections can be treated or prevented by the use of vaccines. For example, the polio vaccine can prevent poliovirus infections. Typically, a vaccine is a suspension of attenuated or killed microorganisms.
IgE-related diseases are mediated by a class of immunoglobulin designated as immunoglobulin E (IgE). In fact, IgE antibodies are a major cause of hypersensitivity reactions found within the human population despite their normally very low concentration in human plasma (10-400 ng/mL). The effects are due to the interaction of IgE antibodies with the high-affinity receptor for IgE on mast cells and basophilic leukocytes. Cross-linking of two IgE receptors on the surface of these cell types, for example by allergen binding, initiates the release of a number of physiologically active substances such as histamine, PAF platelet activating factor), heparin, leukotrienes, prostaglandins, thromboxanes, and chemotactic factors for eosinophilic and neutrophilic granulocytes. Presumably, these mediators cause the direct symptoms of IgE-mediated allergic reactions (type I hypersensitivity). Disease conditions belonging to this group can include asthma, far allergies, pollen allergies, food allergies, and eczema.
The high-affinity receptor for IgE has been characterized. This receptor appears to be present on mast cells, basophilic leucocytes, eosinophils, monocytes, and Langerhan cells. In addition, the receptor is a complex of three different subunits (α, β, and γ chains). The α chain is localized mainly extra-cellularly and appears to interact with the IgE molecule. Previous studies of the epsilon chain of the IgE molecule have suggested that a region of 76 amino acids at the border between the CH2 and CH3 domains (CH refers to the constant domains in the heavy chain) is important for the interaction between the IgE molecule and its high-affinity receptor. In addition, a peptide corresponding to this region was shown to inhibit the interaction between native IgE and its high-affinity receptor in vitro at a molar ratio of nearly 1:1 compared to the whole CH2-CH3-CH4 region (Helm et al., Nature 331, 180-183 (1988)). This peptide was also shown to inhibit an IgE-mediated flare reaction in allergen stimulation. In this case, however, the concentration was about 10 times the concentration needed to exhibit the same inhibitory effect with native IgE (Helm et al., Proc. Natl. Acad. Sci. USA 86, 9465-9469 (1989)).